ArticleAmerican journal of medical genetics. Part A2019
Novel homozygous ENPP1 mutation causes generalized arterial calcifications of infancy, thrombocytopenia, and cardiovascular and central nervous system syndrome.
Article in American journal of medical genetics. Part A, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Optimizing diagnosis and management of patients with ENPP1 deficiency: an expert opinion.Journal of endocrinological investigation · 2026Review
- NovelNeurosciences (Riyadh, Saudi Arabia) · 2026Article
- Article
- Six cases ofJBMR plus · 2025Article
- Article
- A 3-month-old Infant with Mottled Hypo- and Hyper-pigmented Patches on the Extremities: A Quiz.Acta dermato-venereologica · 2024Article
- Mutation update: Variants of the ENPP1 gene in pathologic calcification, hypophosphatemic rickets, and cutaneous hypopigmentation with punctate keratoderma.Human mutation · 2022Review
- Case Report: Coexistence of generalized arterial calcification of infancy (GACI) and maternal infections with cytomegalovirus andFrontiers in pediatrics · 2022Article
- Case Report and Review of Literature: Autosomal Recessive Hypophosphatemic Rickets Type 2 Caused by a Pathogenic Variant inFrontiers in endocrinology · 2022Review
- Generalized Arterial Calcification of Infancy Type 1 (GACI1): Identification of a Novel Pathogenic Variant (c.1715T>C (p.Leu572Ser)).Diagnostics (Basel, Switzerland) · 2021Article
- Case Report: A Novel Genetic Mutation Causes Idiopathic Infantile Arterial Calcification in Preterm Infants.Frontiers in genetics · 2021Article
- Consensus Recommendations for the Diagnosis and Management of X-Linked Hypophosphatemia in Belgium.Frontiers in endocrinology · 2021Review
- Validation of a next-generation sequencing (NGS) panel to improve the diagnosis of X-linked hypophosphataemia (XLH) and other genetic disorders of renal phosphate wasting.European journal of endocrinology · 2020Article
- Generalized Arterial Calcification of Infancy: New Insights, Controversies, and Approach to Management.Current osteoporosis reports · 2020Review
- ENPP1, an Old Enzyme with New Functions, and Small Molecule Inhibitors-A STING in the Tale of ENPP1.Molecules (Basel, Switzerland) · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
Generalized arterial calcifications of infancy (GACI) is caused by mutations in ENPP1. Other ENPP1-related phenotypes include pseudoxanthoma elasticum, hypophosphatemic rickets, and Cole disease. We studied four children from two Bedouin consanguineous families who presented with severe clinical phenotype including thrombocytopenia, hypoglycemia, hepatic, and neurologic manifestations. Initial working diagnosis included congenital infection; however, patients remained without a definitive diagnosis despite extensive workup. Consequently, we investigated a potential genetic etiology. Whole exome sequencing (WES) was performed for affected children and their parents. Following the identification of a novel mutation in the ENPP1 gene, we characterized this novel multisystemic presentation and revised relevant imaging studies. Using WES, we identified a novel homozygous mutation (c.556G > C; p.Gly186Arg) in ENPP1 which affects a highly conserved protein domain (somatomedin B2). ENPP1-associated genetic diseases exhibit phenotypic heterogeneity depending on mutation type and location. Follow-up clinical characterization of these families allowed us to revise and detect new features of systemic calcifications, which established the diagnosis of GACI, expanding the phenotypic spectrum associated with ENPP1 mutations. Our findings demonstrate that this novel ENPP1 founder mutation can cause a fatal multisystemic phenotype, mimicking severe congenital infection. This also represents the first reported mutation affecting the SMB2 domain, associated with GACI.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.